Suppression of Cytomegalovirus Retinitis Utilizing High Dose Intravenous Acyclovir and Oral Zidovudine in Patients With AIDS

October 26, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To study the use of acyclovir (ACV) and zidovudine (AZT) in the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS who would otherwise be treated with ganciclovir (DHPG) alone.

CMV retinitis is one of the most common opportunistic infections in patients with AIDS. DHPG is at present the only drug available for widespread compassionate use in the United States. Although most patients respond to treatment with DHPG, the medication does not cure the infection. Most patients will have a relapse and will require retreatment with DHPG. Because of the large relapse rate, most people treated for CMV retinitis are placed on continuous treatment with DHPG. There are two major problems associated with ongoing use of DHPG: 1) The development of a low white blood cell (WBC) count (leukopenia) which is a known side effect of the drug; and 2) the increased risk for leukopenia when DHPG is given together with AZT, the only antiviral drug currently available for the treatment of HIV infection. Therefore, patients cannot take both AZT and DHPG at the same time because the bone marrow toxicity is made much more severe when the drugs are given together. This has resulted in the difficult decision as to whether to forgo potential life-extending therapy with AZT in order to preserve sight. An effective treatment for CMV retinitis is needed that will allow the patient to also take AZT. ACV is presently the drug of choice for severe herpes virus infections. It has been shown to be effective in suppressing severe CMV disease in patients who have received bone marrow transplants.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

CMV retinitis is one of the most common opportunistic infections in patients with AIDS. DHPG is at present the only drug available for widespread compassionate use in the United States. Although most patients respond to treatment with DHPG, the medication does not cure the infection. Most patients will have a relapse and will require retreatment with DHPG. Because of the large relapse rate, most people treated for CMV retinitis are placed on continuous treatment with DHPG. There are two major problems associated with ongoing use of DHPG: 1) The development of a low white blood cell (WBC) count (leukopenia) which is a known side effect of the drug; and 2) the increased risk for leukopenia when DHPG is given together with AZT, the only antiviral drug currently available for the treatment of HIV infection. Therefore, patients cannot take both AZT and DHPG at the same time because the bone marrow toxicity is made much more severe when the drugs are given together. This has resulted in the difficult decision as to whether to forgo potential life-extending therapy with AZT in order to preserve sight. An effective treatment for CMV retinitis is needed that will allow the patient to also take AZT. ACV is presently the drug of choice for severe herpes virus infections. It has been shown to be effective in suppressing severe CMV disease in patients who have received bone marrow transplants.

Patients receive ACV intravenously and AZT orally for 12 weeks. Tolerance of the combined administration of ACV and AZT is monitored. AMENDED: AZT dose lowered and inclusion of concurrent medication expanded.

Study Type

Interventional

Enrollment

25

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Univ Med School
      • Chicago, Illinois, United States, 60612
        • Rush Presbyterian - Saint Luke's Med Ctr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Prior Medication:

Required:

  • Patients must have successfully completed remission induction therapy with ganciclovir (minimum of 14 days of therapy) for acute cytomegalovirus (CMV) retinitis within the preceding 48 hours. Patients who show no evidence of progressive disease are considered to have met criteria for successful induction.

Amended to allow:

  • Investigational triazoles.
  • Human recombinant erythropoietin (Eprex).
  • Other investigational non-antiviral therapies offered through treatment IND.

Patients must:

  • Have HIV infection as determined by a commercially licensed ELISA test confirmed by a licensed Western blot
  • Have salvageable vision (corrected acuity of 20/100 or better) in at least one eye.
  • Be capable of signing an informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Known or suspected allergy to one of the study medications.
  • Inability to maintain adequate hydration status.

Concurrent Medication:

Excluded:

  • Concurrent therapy with nephrotoxic agents.
  • Systemic therapy for another opportunistic infection.
  • Systemic prophylaxis for Pneumocystis carinii pneumonia (PCP).
  • Probenecid.
  • Patients are advised that validity of this trial may be jeopardized by use of other potentially antiviral or immunomodulating treatments.

Patients with the following are excluded:

  • Known or suspected allergy to one of the study medications.
  • Inability to maintain adequate hydration status.

Prior Medication:

Excluded within 2 weeks of study entry:

  • Steroids.
  • Cytotoxic or immunosuppressive drugs.
  • Investigational agents. (Amended to now allow these.) Immunomodulatory drugs (except ganciclovir).

Prior Treatment:

Excluded within 2 weeks of study entry:

  • Radiotherapy.

Risk Behavior:

Excluded:

  • History of unreliable drug intake and inability to cooperate in the testing procedures. Unwilling or unable to give informed consent or unwilling to sign approved consent form.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: HA Kessler
  • Study Chair: CA Benson

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

March 1, 1992

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

November 2, 2021

Last Update Submitted That Met QC Criteria

October 26, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 070
  • 11044 (Registry Identifier: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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